Interleukin-10 in acute respiratory virus infection

白介素10在急性呼吸道病毒感染中的作用

• 批准号: 7746088
• 负责人: Thomas J Braciale
• 金额: $ 24.83万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-18 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7746088
• 关键词: Acute; Anti-Inflammatory Agents; Anti-inflammatory; Body Surface; CD8B1 gene; Cells; Collaborations; Companions; Complement; Complex; Cytomegalovirus Infections; Dendritic Cells; Development; Dose; Foundations; Generations; Goals; Human; Immune; Immune response; Immune system; Infection; Inflammation; Inflammatory; Inflammatory Response; Influenza; Influenza A Virus, H5N1 Subtype; Injury; Interleukin-10; Intervention; Laboratories; Liver; Lung; Lung Inflammation; Mediating; Mediator of activation protein; Modeling; Mononuclear; Murid herpesvirus 1; Mus; Natural Killer Cells; Organ; Outcome; Phase; Phenotype; Play; Pneumonia; Process; Production; Property; Proteins; Recovery; Regulation; Reporter; Research Design; Respiratory System; Respiratory Tract Infections; Respiratory tract structure; Role; SARS coronavirus; Severities; Signal Transduction; Site; Source; Structure of parenchyma of lung; Surface; T-Lymphocyte; Techniques; Testing; Tissues; Type A Influenza; Viral; Virus; Virus Diseases; Virus Replication; cell motility; cell type; chemokine; cost; cytokine; design; influenzavirus; insight; lung injury; macrophage; monocyte; receptor; research study; respiratory; respiratory infection virus; response

Pulmonary inflammation and injury is a frequent (and, in some instances, lethal) outcome of virus infections of the respiratory tract. Respiratory virus infection triggers a coordinated response from the host innate and adaptive immune systems. The host response is essential for virus clearance and recovery, but is also a significant cause of pulmonary injury that can accompany virus elimination. Relevant recent examples of this are the immune-mediated lung inflammation/injury observed in human infections with the SARS coronavirus and the H5N1 avian influenza viruses. The long-term goal of Project 1 is to define and characterize the interactions between cells of the innate immune system i.e. dendritic cells, monocyte/ macrophage, NK cells and adaptive immune effector T lymphocytes (Tej in the process of virus clearance and in the control of inflammation/injury during experimental virus infection of the respiratory tract. The foundation for this application is our recent and unexpected findings in the murine model of type A influenza infection that anti-viral effector T-cells (both CD4 +Te and more prominently CDS +Te) infiltrating the infected lungs produce high levels of the anti-inflammatory/regulatory cytokines IL-10 during the Te response to infection and virus elimination. Furthermore, we found that blocking the effect of Te-derived IL- 10 during infection results in increased pulmonary inflammation and lethal injury. Our evidence further suggests that this Te-derived IL-10 plays a central role in controlling the level of lung inflammation/injury produced by mononuclear cells infiltrating the infected lungs in response to virus infection and the proinflammatory mediators released by virus- immune (Te). We wish to analyze the expression and regulation of IL-10 and specifically Te-derived IL-10 in the infected lungs and the impact of this cytokine on the control of virus clearance and lung inflammation/injury. The aims of Project 1 are: 1. To evaluate the cellular sources and effects of IL-10 on influenza virus infection; 2. To analyze the regulation of IL-10 production by Te during influenza infection; 3. To determine the impact of viral infection on the production of Te-derived IL- 10. The proposed studies are designed to complement ongoing related studies in Projects 2, 3 and 4.

肺部炎症和损伤是病毒感染的常见（在某些情况下甚至是致命的）结果 呼吸道的。呼吸道病毒感染会触发宿主先天和体内的协调反应 适应性免疫系统。宿主反应对于病毒清除和恢复至关重要，但也是一种 伴随病毒消除的肺损伤的重要原因。最近的相关例子 是在人类感染 SARS 冠状病毒时观察到的免疫介导的肺部炎症/损伤 和 H5N1 禽流感病毒。项目 1 的长期目标是定义和描述 先天免疫系统细胞之间的相互作用，即树突状细胞、单核细胞/巨噬细胞、NK 细胞 和适应性免疫效应T淋巴细胞（Tej）在病毒清除过程中和控制 呼吸道实验性病毒感染期间的炎症/损伤。 该应用的基础是我们最近在 A 型小鼠模型中的意外发现 抗病毒效应 T 细胞（CD4 + Te 和更显着的 CDS + Te）浸润的流感感染 受感染的肺部在 Te 期间产生高水平的抗炎/调节细胞因子 IL-10 对感染和病毒消除的反应。此外，我们发现阻断Te衍生的IL-的作用 10 感染期间会导致肺部炎症加剧和致命伤害。我们的证据进一步 表明这种 Te 衍生的 IL-10 在控制肺部炎症/损伤水平方面发挥着核心作用 由渗透受感染肺部的单核细胞产生，以响应病毒感染和促炎反应 病毒免疫（Te）释放的介质。我们希望分析表达和调节 受感染肺部中 IL-10（特别是 Te 衍生的 IL-10）的含量以及该细胞因子对对照的影响 病毒清除和肺部炎症/损伤。项目 1 的目标是： 1. 评估细胞 IL-10的来源及其对流感病毒感染的影响； 2. 分析IL-10产生的调控 流感感染期间的Te； 3. 确定病毒感染对 Te 衍生 IL- 产生的影响 10. 拟议研究旨在补充项目 2、3 和 4 中正在进行的相关研究。